In biomedical applications (such as therapeutic drug delivery), it is of paramount importance to be able to measure the nanoscale distribution of biological molecules (ligands, for ligand-receptor interaction) on biological surfaces (of the nanoparticles carrying drugs). This allows researchers to produce new medicines that will cure diseases that have resisted till today treatment. To this end, from a technological perspective, new powerful microscopes where developed and are nowadays used to study these surfaces with single molecule resolution. Based on the information obtained from the microscope, it is the work of a statistician to determine the distribution accounting for the chemical properties.
In our recently published work, we study homogeneity of fluorescent molecules on spherical nanoparticle beads using direct stochastic optical reconstruction microscopy (dSTORM) measurements. We developed a mathematical model to describe the dSTORM dynamics to efficiently recover the source locations. Additionally, the model has been used to create computer-generated synthetic dSTORM measurements of homogeneously functionalized nanoparticles that can be used as a comparison. Stochastic fluctuations proved insufficient to explain the experimentally observed variability and the, commonly assumed, hypothesis of stochastically homogeneous (“fully random”) attachment of functionalities was rejected for these experimental beads. More generally, these results cast doubt on the uniform surface coverage commonly assumed in the creation of functional nanoparticles.
This talk is based on joint work with colleagues from the TU/e biochemistry department that recently appeared in nature communications ( article ) and reflect on the interdisciplinary collaboration. A popular scientific blog on this research can be found here .